, Volume 117, Issue 1, pp 2–10 | Cite as

The scientific case that nicotine is addictive

  • I. P. Stolerman
  • M. J. Jarvis


Despite the wide-ranging and authoritative 1988 review by the US Surgeon General, views questioning the addictiveness of nicotine contine to be expressed in some quarters. This lack of complete consensus is not unexpected, since no universally agreed scientific definition of addiction exists. In this paper we briefly consider a number of lines of evidence from both the human and animal literature bearing on the addictiveness of nicotine. Patterns of use by smokers and the remarkable intractability of the smoking habit point to compulsive use as the norm. Studies in both animal and human subjects have shown that nicotine can function as reinforcer, albeit under a more limited range of conditions than with some other drugs of abuse. In drug discrimination paradigms there is some cross-generalisation between nicotine on the one hand, and amphetamine and cocaine on the other. A well-defined nicotine withdrawal syndrome has been delineated which is alleviated by nicotine replacement. Nicotine replacement also enhances outcomes in smoking cessation, roughly doubling success rates. In total, the evidence clearly identifies nicotine as a powerful drug of addiction, comparable to heroin, cocaine and alcohol.

Key words

Tobacco use Nicotine Addiction 


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  1. American Psychiatric Association, (1987) Diagnostic and statistical manual of mental disorders, 3rd edn. Washington DCGoogle Scholar
  2. Ando K, Yanagita T (1978) The discriminative stimulus properties of intravenously administered cocaine in rhesus monkeys. In: Colpaert FC, Rosecrans JA (eds) Stimulus properties of drugs: ten years of progress. Elsevier/North-Holland, Amsterdam, pp 125–136Google Scholar
  3. Ator NA, Griffiths PR (1981) Intravenous self-administration of nicotine in the baboon. Fed Proc 40:298Google Scholar
  4. Babor TF (1990) Social, scientific and medical issues in the definition of alcohol and drug dependence. In: Edwards G, Lader MH (eds) The nature of drug dependence. Oxford University Press, Oxford, pp 19–36Google Scholar
  5. Benwell MEM, Balfour DJK (1992) The effects of acute and repeated nicotine treatment on nucleus accumbens dopamine and locomotor activity. Br J Pharmacol 105:849–856PubMedGoogle Scholar
  6. Bigelow G, Rand CS, Gross J, Barling TA, Gotlieb SH (1963) Smoking cessation and relapse among cardiac patients. In: Tims FM, Leubefeld CG (eds) Relapse and recovery in drug abuse. NIDA Research Monograph 72. Department of Health and Human Services, Rockville, MarylandGoogle Scholar
  7. Brazell MP, Mitchell SN, Joseph MH, Gray JA (1990) Acute administration of nicotine increases thein vivo extracellular levels of dopamine, 3,4-dihydroxyphenylacetic acid and ascorbic acid preferentially in the nucleus accumbens of the rat: comparison with caudate-putamen. Neuropharmacology 29:1177–1185CrossRefPubMedGoogle Scholar
  8. Chait LD, Johanson C-E (1988) Discriminative stimulus effects of caffeine and benzphetamine in amphetamine trained volunteers. Psychopharmacology 96:302–308Google Scholar
  9. Chance WT, Murfin D, Krynock GM, Rosecrans JA (1977) A description of the nicotine stimulus and tests of its generalization to amphetamine. Psychopharmacology 55:19–26CrossRefGoogle Scholar
  10. Clarke PBS, Kumar R (1984) Effects of nictonie andd-amphetamine on intracranial self-stimulation in a shuttlebox test in rats. Psychopharmacology 84:109–114CrossRefPubMedGoogle Scholar
  11. Cohen S, Lichtenstein E, Prochaska JO et al. (1989) Debunking myths about self-quitting. Am Psychol 44:1355–1365CrossRefPubMedGoogle Scholar
  12. Corrigall WA, Herling S, Coen KM (1989) Evidence for a behavioral deficit during withdrawal from chronic nicotine treatment. Pharmacol Biochem Behav 33:559–562Google Scholar
  13. Corrigall WA, Franklin KBJ, Coen KM, Clarke PBS (1992) The mesolimbic dopaminergic system is implicated in the reinforcing effects of nicotine. Psychopharmacology 107:285–289PubMedGoogle Scholar
  14. Davison G, Duffy M (1982) Smoking habits of long-term survivors of surgery for lung cancer. Thorax 37:331–333PubMedGoogle Scholar
  15. de la Garza R, Johanson CE (1983) The discriminative stimulus properties of cocaine in the rhesus monkey. Pharmacol Biochem Behav 19:145–148CrossRefPubMedGoogle Scholar
  16. de la Garza R, Johanson CE (1985) Discriminative stimulus properties of cocaine in pigeons. Psychopharmacology 85:23–30CrossRefPubMedGoogle Scholar
  17. Druhan JP, Fibiger HC, Phillips AG (1991) Influence of some drugs of abuse on the discriminative stimulus properties of amphetamine. Behav Pharmacol 2:391–403PubMedGoogle Scholar
  18. Fagerström KO, Schneider NG, Lunell E (1993) Effectiveness of nicotine patch and nicotine gum as individual versus combined treatments for tobacco withdrawal symptoms. Psychopharmacology 111:271–277CrossRefPubMedGoogle Scholar
  19. Foulds J (1993) Does nicotine replacement therapy work? Addiction 88:1473–1478PubMedGoogle Scholar
  20. Gauvin DV, Harland RD, Michaelis RC, Holloway FA (1989) Caffeine phenylethylamine combinations mimic the cocaine discriminative cue. Life Sci 44:67–73CrossRefPubMedGoogle Scholar
  21. Gawin FH (199) Cocaine addiction: psychology and neurophysiology. Science 251:1580–1586Google Scholar
  22. Goddard E (1990) Why children start smoking. HMSO, LondonGoogle Scholar
  23. Goldberg SR (1973) Comparable behavior maintained under fixed-ratio and second-order schedules of food presentation, cocaine injection ord-amphetamine injection in the squirrel monkey. J Pharmacol Exp Ther 186:18–30PubMedGoogle Scholar
  24. Goldberg SR (1975) Stimuli associated with drug injections as events that control behavior. Pharmacol Rev 27:325–340PubMedGoogle Scholar
  25. Goldberg SR, Spealman RD (1982) Maintenance and suppression of behavior by intravenous nicotine injections in squirrel monkeys. Fed Proc 41:216–220PubMedGoogle Scholar
  26. Goldberg SR, Spealman RD, Goldberg DM (1981) Persistent behavior at high rates maintained by intravenous self-administration of nicotine. Science 214:573–575PubMedGoogle Scholar
  27. Goudie AJ, Leathley MJ (1993) Drug discrimination assays. In: Sahgal A (ed) Behavioural neuroscience. Open University Press, Walton Hall, Bucks. pp 145–167Google Scholar
  28. Griffiths RR, Brady JV, Bradford LD (1979) Predicting the abuse liability of drugs with animal drug self-administration procedures: psychomotor stimulants and hallucinogens. In: Thompson T, Dews PB (eds) Advances in behavioral pharmacology, Vol 2. Academic Press, New York, pp 162–208Google Scholar
  29. Gross J, Stitzer ML (1989) Nicotine replacement: ten-week effects on tobacco withdrawal symptoms. Psychopharmacology 98:334–341CrossRefPubMedGoogle Scholar
  30. Harland RD, Gauvin DV, Michaelis RC, Carney JM, Seale TW, Holloway FA (1989) Behavioral interaction between cocaine and caffeine: a drug discrimination analysis in rats. Pharmacol Biochem Behav 32:1017–1023Google Scholar
  31. Harris CM, Emmett-Oglesby MW, Robinson NG, Lal H (1986) Withdrawal from chronic nicotine substitutes partially for the interoceptive stimulus produced by pentylenetetrazol (PTZ). Psychopharmacology 90:85–89Google Scholar
  32. Hatsukami DK, Gust SW, Keenan RM (1987) Physiologic and subjective changes from smokeless tobacco withdrawal. Clin Pharmacol Ther 41:103–107PubMedGoogle Scholar
  33. Henningfield JE, Goldberg SR (1984) Stimulus properties of nicotine in animals and human volunteers: a review. In: Seiden LS, Balster RL (eds). Behavioral pharmacology: the current status. Alan R Liss, New York, pp 433–449Google Scholar
  34. Himbury S, West R (1984) Smoking habits after laryngectomy. BMJ 291:514–515Google Scholar
  35. Hughes JR (1992) Tobacco withdrawal in self-quitters. J Consult Clin Psychol 60:689–697CrossRefPubMedGoogle Scholar
  36. Hughes JR (1993) Smoking is a drug dependence: a reply to Robinson and Pritchard. Psychopharmacology 113:282–283CrossRefPubMedGoogle Scholar
  37. Hughes JR, Hatsukami D (1986) Signs and symptoms of tobacco withdrawal. Arch Gen Psychiatry 43:289–294PubMedGoogle Scholar
  38. Hughes JR, Hatsukami DK, Pickens RW, Krahn D, Malin S, Luknic A (1984) Effect of nicotine on the tobacco withdrawal syndrome. Psychopharmacology 83:82–87CrossRefPubMedGoogle Scholar
  39. Hughes JR, Hatsukami DK Skoog K (1986) Physical dependence on nicotine gum: a placebo substitution trial JAMA 255:3277–3279CrossRefPubMedGoogle Scholar
  40. Hughes JR, Higgins ST, Hatsukami DK (1990) Effects of abstinence from tobacco: a critical review. In: Kozlowski LT, Annis HM, Cappell HD, Glaser FB, Goodstadt MS, Israel Y, Kalant H, Sellers EM, Vingilis J (eds) Research advances in alcohol and drug problems, Vol 10. Plenum, New York, pp 317–398Google Scholar
  41. Hughes JR, Gulliver SB, Fenwick JW, Valliere WA, Cruser K, Pepper S, Shea P, Solomon LJ, Flynn BS (1992) Smoking cessation among self-quitters. Health Psychol 11:331–334CrossRefPubMedGoogle Scholar
  42. Hunt WA, Bespalec DA (1974) An evaluation of current methods of modifying smoking behaviour. J Clin Psychol 30:431–438PubMedGoogle Scholar
  43. Hunt WA, Barnett LW, Branch LG (1971) Relapse rates in addiction programs. J Clin Psychol 27:455–456PubMedGoogle Scholar
  44. Huston-Lyons D, Kornetsky C (1992) Effects of nicotine on the threshold for rewarding brain stimulation in rats. Pharmacol Biochem Behav 41:755–759CrossRefPubMedGoogle Scholar
  45. Imperato A, Mulas A, Di Chiara G (1986) Nicotine preferentially stimulates dopamine release in the limbic system of freely moving rats. Eur J Pharmacol 132:337–338Google Scholar
  46. Jaffe JH (1990) Tobacco smoking and nicotine dependence. In: Wonnacott S, Russell MAH, Stolerman IP (eds) Nicotine psychopharmacology: molecular, cellular and behavioural aspects. Oxford Science Publications, Oxford, pp 1–37Google Scholar
  47. Jarvis MJ, Raw M, Russell MAH, Feyerabend C (1982) Randomised controlled trial of nicotine chewing-gum. BMJ 285:537–540PubMedGoogle Scholar
  48. Johanson CE (1978) Drugs as reinforcers. In: Blackman DE, Sanger DJ (eds) Contemporary research in behavioral pharmacology. Plenum, New York, pp 325–390Google Scholar
  49. Jones RT (1992) What we have learned from nicotine, cocaine and marijuana about addiction. In: O'Brien CP, Jaffe JH (eds) Addictive states. Res Publ Assoc Res Nerv Ment Dis Vol 70. Raven, New York, pp 109–122Google Scholar
  50. Karler R, Calder LD, Chaudry IA, Turkanis SA (1989) Blockade of “reverse tolerance” to cocaine and amphetamine by MK-801. Life Sci 45:599–606CrossRefPubMedGoogle Scholar
  51. Ksir C, Hakan RL, Kellar KJ (1987) Chronic nicotine and locomotor activity: influences of exposure dose and test dose. Psychopharmacology 92:25–29CrossRefPubMedGoogle Scholar
  52. Levin ED, Rose JE (1990) Anticholinergic sensitivity following chronic nicotine administration as measured by radial-arm maze performance in rats. Behav Pharmacol 1:511–520PubMedGoogle Scholar
  53. Malin DH, Lake JR, Newlin-Maultsby P, Roberts LK, Lanier JG, Carter VA, Cunningham JS, Wilson OB (1992) Rodent model of nicotine abstinence syndrome. Pharmacol Biochem Behav 43:779–784CrossRefPubMedGoogle Scholar
  54. Mariathasan EA, Stolerman IP (1992) Drug discrimination studies in rats with caffeine and phenylpropanolamine administered separately and as mixtures. Psychopharmacology 109:99–106CrossRefPubMedGoogle Scholar
  55. Marks MJ, Burch JB, Collins AC (1983) Effects of chronic nicotine infusion on tolerance development and nicotinic receptors. J Pharmacol Exp Ther 226:817–825PubMedGoogle Scholar
  56. Marks MJ, Stitzel JA, Collins AC (1985) Time course study of the effects of chronic nicotine infusion on drug responses and brain receptors. J Pharmacol Exp Ther 235:619–628PubMedGoogle Scholar
  57. Modrow HE, Holloway FA, Carney JM (1981) Caffeine discrimination in the rat. Pharmacol Biochem Behav 14:683–688CrossRefPubMedGoogle Scholar
  58. Mumford GK, Holtzman SG (1991) Qualitative differences in the discriminative stimulus effects of low and high doses of caffeine in the rat. J Pharmacol Exp Ther 258:857–865PubMedGoogle Scholar
  59. NOP Omnibus Services (1992) Smoking habits 1991: a report prepared for the Department of Health. Department of Health, LondonGoogle Scholar
  60. Risner ME, Goldberg SR (1983) A comparison of nicotine and cocaine self-administration in the dog: fixed-ratio and progressive-ratio schedules of intravenous drug infusion. J Pharmacol Exp Ther 224:319–326PubMedGoogle Scholar
  61. Roberts DCS, Koob GF, Klonoff P, Fibiger HC (1980) Extinction and recovery of cocaine self-administration following 6-hydroxydopamine lesions of the nucleus accumbens. Pharmacol Biochem Behav 12:781–787Google Scholar
  62. Robins LN (1993) Vietnam veterans' rapid recovery from heroin addiction: a fluke or normal expectation. Addiction 88:1041–1054PubMedGoogle Scholar
  63. Robinson JH, Pritchard WS (1992) The role of nicotine in tobacco use. Psychopharmacology 108:397–407CrossRefPubMedGoogle Scholar
  64. Rowell PP, Carr LA, Garner AC (1987) Stimulation of [3H]dopamine release by nicotine in rat nucleus accumbens. J Neurochem 49:1449–1454PubMedGoogle Scholar
  65. Russell MAH (1974) The smoking habit and its classification. Practitioner 212:791–800PubMedGoogle Scholar
  66. Russell MAH (1986) Conceptual Framework for nicotine substitution. In: Ockene JK (ed) The pharmacologic treatment of tobacco dependence: Proceedings of the World Congress. Cambridge, Massachusetts, Harvard University Institute for the Study of Smoking Behavior and Policy, pp 90–107Google Scholar
  67. Russell MAH, Stapleton J, Feyerbend C, Wiseman SM, Gustavsson G (1993) Targeting heavy smokers in general practice: randomised controlled trial of transdermal nicotine patches. BMJ 306:1308–1312PubMedGoogle Scholar
  68. Schaefer GJ, Michael RP (1986) Task-specific effects of nicotine in rats. Intracranial self-stimulation and locomotor activity. Neuropharmacology 25:125–131CrossRefPubMedGoogle Scholar
  69. Schuster CR, Thompson T (1969) Self-administration of and behavioral dependence on drugs. Annu Rev Pharmacol 9:483–502CrossRefPubMedGoogle Scholar
  70. Schwartz, JL (1987) Review and evaluation of smoking cessation methods: the United States and Canada 1978–985. US Department of Health and Human Services, Washington DCGoogle Scholar
  71. Shiffman S (1989) Tobacco chppers — individual differences in tobacco dependence. Psychopharmacology 97:539–547Google Scholar
  72. Shoaib M, Stolerman IP (1992) MK801 attenuates behavioural adaptation to chronic nicotine administration in rats. Br J Pharmacol 105:514–515PubMedGoogle Scholar
  73. Shoaib M, Benwell MEM, Akbar MT, Stolerman IP, Balfour DJK (1994) Behavioural and neurochemical adaptations to nicotine in rats: influence of NMDA antagonists. Br J Pharmacol 111:1073–1080PubMedGoogle Scholar
  74. Silverman PB, Schultz KA (1989) Comparison of cocaine and procaine discriminative stimuli. Drug Dev Res 16:427–433CrossRefGoogle Scholar
  75. Smyth, M, Browne, F (1992) General household survey 1990. HMSO, LondonGoogle Scholar
  76. Stolerman IP (1987) Psychopharmacology of nicotine: stimulus effects and receptor mechanisms. In: Iversen LL, Iversen SD, Snyder SH (eds) Handbook of psychopharmacology, Vol. 19. Plenum, New York, pp 421–465Google Scholar
  77. Stolerman IP (1989) Discriminative stimulus effects of nicotine in rats trained under different schedules of reinforcement. Psychopharmacology 97:131–138CrossRefGoogle Scholar
  78. Stolerman IP, Garcha HS, Pratt JA, Kumar R (1984) Role of training dose in discrimination of nicotine and related compounds by rats. Psychopharmacology 84:413–419CrossRefGoogle Scholar
  79. Sutherland G, Stapleton J, Russell MAH, Jarvis MJ, Hajek P, Belcher M, Feyerabend C (1992) Randomised controlled trial of nicotine nasal spray in smoking cessation. Lancet 340:324–329CrossRefPubMedGoogle Scholar
  80. Swedberg MDB, Henningfield JE, Goldberg SR (1990) Nicotine dependency: animal studies. In: Wonnacott S, Russell MAH, Stolerman IP (eds) Nicotine psychopharmacology: molecular, cellular and behavioural aspects. Oxford Science Publications, Oxford, pp 38–76Google Scholar
  81. Tonnesen P, Norregaard J, Simonsen K, Säwe U (1991) A doubleblind trial of a 16-hour nicotine patch in smoking cessation. N Engl J Med 325:311–315PubMedGoogle Scholar
  82. Tonnesen P, Norregaard J, Mikkelsen K, Jorgensen S, Nilsson F (1993) A double-blind trial of a nicotine inhaler for smoking cessation. JAMA 269:1268–1271CrossRefPubMedGoogle Scholar
  83. Transdermal Nicotine Study Group (1991) Transdermal nicotine for smoking cessation: six-month results from two multicenter controlled clinical trials. JAMA 266:3133–3138Google Scholar
  84. Trujillo KA, Akil H (1991) Inhibition of morphine tolerance and dependence by the NMDA receptor antagonist MK-801. Science 251:85–87Google Scholar
  85. US Department of Health, Education and Welfare (1964) Smoking and Health. Report of the Advisory Committee to the Surgeon General of the Public Health Service. US Department of Health, Education and Welfare, Washingtone, DCGoogle Scholar
  86. US Department of Health and Human Services (1988) The health consequences of smoking: nicotine addiction. A Report of the Surgeon General. Office on Smoking and Health, MarylandGoogle Scholar
  87. Warburton DM (1989) Is nicotine use an addiction? Psychologist 4:166–170Google Scholar
  88. Warburton DM (1990) Heroin, cocaine and now nicotine. In: Warburton DM (ed) Addiction controversies. Harwood Academic Publishers, Switzerland, pp 21–35Google Scholar
  89. West RJ (1992a) Nicotine addiction: a re-analysis of the arguments. Psychopharmacology 108:408–410CrossRefPubMedGoogle Scholar
  90. West R (1992b) The “nicotine replacement paradox” in smoking cessation: how does nicotine gum really work? Br J Addict 87:165–167PubMedGoogle Scholar
  91. West RJ, Russell MAH (1985) Effects of withdrawal from long-term nicotine gum use. Psychol Med 15:891–893PubMedGoogle Scholar
  92. West RJ, Jarvis MJ, Russell MAH Carruthers ME, Feyerbend C (1984) Effect of nicotine replacement on the cigarette withdrawal syndrome. Br J Addict 79:215–219PubMedGoogle Scholar
  93. West RJ, Hajek P, Belcher M (1989) Severity of withdrawal symptoms as a predictor of outcome of an attempt to quit smoking. Psychol Med 98:331–334Google Scholar
  94. World Health Organization (1969) World Health Organization Technical Report Series No. 407. WHO, GenevaGoogle Scholar
  95. World Health Organization (1978) International classification of diseases, 9th edn. WHO, GenevaGoogle Scholar
  96. Young AM, Herling S (1986) Drugs as reinforcers: studies in laboratory animals. In: Goldberg SR, Stolerman IP (eds) Behavioral analysis of drug dependence. Academic Press, Orlando, Florida, pp 9–67Google Scholar

Copyright information

© Springer-Verlag 1995

Authors and Affiliations

  • I. P. Stolerman
    • 1
  • M. J. Jarvis
    • 1
  1. 1.Department of PsychiatryInstitute of PsychiatryLondonUK

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